Introduction 1 2 3 4 6 7 5 Since these contradictory results regarding the association between BME and clinical features have been reported, the purpose of our study was to evaluate changes in BME lesions over a 2-year period, and associate them with clinical features. Patients and methods Patients 8 6 9 Clinical assessment 10 MR acquisition Knees were imaged using a transmit-receive four-channel knee coil in a 1.5-T superconducting magnet (Philips Medical Systems, Best, the Netherlands). Each examination consisted of: coronal proton density and T2-weighted dual spin echo (SE) images (with repetition time (TR) of 2,200 ms; echo time (TE) of 20/80 ms; number of excitations per data line (NEX) 2; 5 mm slice thickness; 0.5 mm intersection gap; 160 mm field of view (FOV); 256 × 205 acquisition matrix, 18 slices); sagittal proton density and T2-weighted dual SE images (TR 2,200 ms; TE 20/80 ms; NEX 2; 4 mm slice thickness; 0.4 mm intersection gap; 160 mm (FOV); 256 × 205 acquisition matrix, 20 slices); sagittal 3D T1-weighted spoiled gradient echo (GE) frequency selective fat suppressed images (TR 46 ms; TE 2.5 ms; NEX 1; flip angle 40°; 3.0 mm slice thickness; slice overlap 1.5 mm; no gap; 180 mm (FOV); 256 acquisition matrix, 80 slices); and axial proton density and T2-weighted turbo spin echo (TSE) fat suppressed images (TR 2,500 ms; TE 7.1/40 ms; NEX 2; 2 mm slice thickness; no gap; 180 mm (FOV); 256 acquisition matrix, 62 slices). Total acquisition time (including the initial survey sequence) was 30 min. MR interpretation 11 12 Subchondral cysts were defined as well-defined foci of high signal intensity, with low signal intensity margins, on T2-weighted images, in the bone underlying the joint cartilage. Their greatest dimension was measured and they were graded as follows: grade 0, absent; grade 1, minimal (<3 mm); grade 2, moderate (3–5 mm); grade 3, severe (>5 mm). A total score of the knee was calculated by adding all grades of each cystic lesion in the knee. Maximum possible knee score was 27 (grade 3 times nine anatomic locations). In the total study a maximum of 1638 cystic lesions (182 patients times nine anatomic locations) could be scored. Statistical analysis Odds ratios (ORs) with 99% confidence intervals (CIs) were used to show any association between BME size changes with cystic size changes. The difference in WOMAC scores between patients without BME lesions (group A) and patients with BME lesions (group B: unchanged BME lesions over 2 years; group C: increasing size of BME lesions over 2 years; group D: decreasing size of BME lesions over 2 years) was calculated by linear mixed models in SPSS for Windows, version 12.0 (SPSS, Chicago, Ill.) with a random intercept to adjust for the familial effect within sib pairs. Adjustments were made for age, sex and body mass index (BMI). Estimates of fixed effects were reported with 95% CIs. Results 1 2 1 Table 1 n   At baseline Age years, median (range) 59 (43–76) Female sex, (%) 157 (80%) 2 25.7 (20.2–40.0) n a 71 (39%) Kellgren & Lawrence Score 0/1/2/3/4, No. 59/53/60/10/0  Over 2 years n b 128 (70%) c 54/56/62/10 n b 100 (55%) c 82/60/37/3  At 2 years d 13 (0–99) d 18 (0–99) d 14 (0–98) a b c d n Table 2 n   BME lesions No BME No change Increase Decrease Total Cysts No cyst 1,280 77 38 21 1,416 No change 24 87 24 17 152 Increase 2 11 30 3 46 Decrease 5 5 3 11 24 Totals 1,311 180 95 52 1,638 Fig. 1 a d a b arrow arrowhead c d open arrowhead  2 2 Fig. 2a, b arrow a b  2 3 3 3 Fig. 3 a b Group A Group B Group C Group D Box plots  Discussion The majority (75%) of patients with familial OA at multiple sites have BME lesions visualized when two sequential MR scans are made with a 2-year time interval. In the majority (66%) of these patients with BME lesions, the total size of BME changed over this 2-year time period. Our study also demonstrates that cysts and BME fluctuations are associated. However, no association existed between changes in BME lesions and severity of WOMAC scores after 2 years. 5 13 5 2 7 2 6 5 2 8 1 1 2 In conclusion, BME lesions are shown to be a variable parameter when followed over time in patients with knee OA and are not predictive of pain.